This application represents a competing continuation of the original P30 Center on Gene Therapy for Cystic Fibrosis and other Genetic Diseases from the University of Pennsylvania. The current application builds on the tremendous strengths in gene therapy and cystic fibrosis research at Penn. An important element of our success is the substantial institutional support that has been committed to gene therapy and will continue through the next cycle of this grant. Dr. James M. Wilson remains the Principal Investigator of the grant which is housed administratively within the Gene Therapy Program in the Division of Medical Genetics of the Department of Medicine. The renewal application reflects the evolution of the field of gene therapy and the mandate to broaden the scope of the Center to include molecular and cellular therapies. Appreciating the limitations of current therapeutic strategies and gene transfer technologies, we made a commitment to the development of new molecular therapy approaches with an emphasis on novel and improved vectors. The outcome has been extremely satisfying with the identification of new vectors based on simian adenoviruses and adeno-associated viruses and the creation of new lentiviral pseudotypes. The cores have been modified to reflect the new opportunities in vectors and to assure maximal support of the participating faculty and will include the following: Vector Core, Cell Morphology Core, Bioassay Core, and Animal Models Core. In addition, the Administrative Core will continue to support the Center. A request is made to continue the Pilot and Feasibility Program which has proven to be extremely successful.